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At least 631 records · Page 35Linked to original sources
PubMed1986

The treatment of non-digitalized congestive heart failure patients with a fixed-dose combination of furosemide and spironolactone.

Seventeen non-digitalized congestive heart failure patients were treated with only the fixed-dose combinations of 20 mg furosemide and 50 mg spironolactone or 20 mg furosemide and 100 mg spironolactone, in a daily dose of 1 or 2 capsules, over a 4-week period. The selected patients had a severity rating ranging between Grades III and IV. Ten of these patients had a severe grade of dyspnoea. Assessments were made on the basis of the reduction in cardiac failure score, extent of reduction in oedema, and relief of dyspnoea. Safety variables measured included laboratory, echocardiographic and side-effect monitoring. By the end of the 4-week study period, significant reduction (46% to 51%) in cardiac score and complete relief of dyspnoea with no adverse effects on safety variables were recorded. These results indicate that it is possible to treat patients with congestive heart failure safely with the fixed-dose combination product without the concurrent use of digitalis.

Aged↗
PubMed1986

Effect of spironolactone on acute mountain sickness.

This study examined the effectiveness of spironolactone as a prophylactic agent for the prevention of acute mountain sickness (AMS). Spironolactone, 25 mg PO QID, or placebo was administered to nine subjects in a double-blind, placebo-controlled, crossover design. Medication was given for 48 h prior to and during a 46-h exposure to 427 mm Hg (4570 m) in a hypobaric chamber. Six subjects demonstrated prevention of either the cerebral or respiratory symptoms of AMS during at least one segment of the altitude sojourn.

Acute Disease↗
PubMedDate not supplied

Metabolism of digitoxin in the isolated perfused rat liver. Effect of spironolactone pretreatment.

Livers from either control or spironolactone-treated rats were perfused for a 90-min period with 30% rat blood and 3H-digitoxin. At several time periods throughout perfusation, bile was collected and a sample of blood was removed from the perfusate. Extractions were performed on both blood and bile to determine amount of polar and nonpolar metabolites at 60 min. Polar metabolites were cleaved with beta-glucuronidase and high-pressure liquid chromatography was used to separate the resultant nonpolar metabolites from blood and bile cleaved with beta-glucuronidase. Biliary excretion and perfusate disappearance of 3H-digitoxin were significantly increased in livers taken from spironolactone-pretreated animals. Both polar and nonpolar metabolites in bile were significantly increased in pretreated animals. The majority of polar metabolites produced by livers from both treated and nontreated animals were readily cleaved with beta-glucuronidase. Both biliary excretion and metabolic pattern, obtained from these studies in an isolated perfused rat liver, mimic those seen in the intact rat. Thus, the isolated perfused rat liver can be used as a model for in vivo studies of cardiac glycoside metabolism.

Animals↗
PubMed1979

Response to nor-epinephrine, isoprenaline and spironolactone derivatives in normal and hypertensive rats.

In normal as well as in experimentally hypertensive rats the Blood Pressure and Heart Rate response-time curves are investigated following administration of nor-epinephrine, isoprenaline, spironolactone and K-canrenoate. The results stress the pharmacological effect dependence on integrity of homeostatic blood pressure mechanisms. alpha and beta receptor systems, as well as renine-angiotensine-aldo sterone system show different response-kinetic in mononefrectomized and mononefrectomized plus controlateral renal stenosis rats (Grollmann's model), in comparison with normal. While in normal rats the spironolactones evoke an hypertensive effect in experimentally renal hypertensive rats they reduce pressure to normal values.

Animals↗
PubMed1979

[Comparative study of relative biovailability of several spironolactone formulations in a steady-state test (author's transl)].

By the US Food and Drug Administration spironolactone is regarded as a drug with problems related to bioavailability. A steady-state study was performed comparing the 50- and 100-mg formulations of two manufacturers with each other. Applying a fluorimetric method to both canrenone and canrenoate--the major biologically active metabolites of spironolactone--the two brands were compared in 11 volunteers for the 50 mg, and in 10 volunteers for the 100 mg dosage form.

Adult↗
PubMed1977

[Hyperammonemia and hepatic encephalopathy in cirrhotics receiving spironolactone (author's transl)].

The aim of this study was to specify the mechanism of hepatic encephalopathy which may occur in some cirrhotics treated by Spironolactone. In 31 cirrhotics with ascite, this diuretic induced a significant increase in arterial ammonemia; 8 patients developed an impending hepatic coma which was associated with ammonemia levels significantly higher than those observed in the patients without encephalopathy at the end of the treatment. Hyperammonemia induced by Spironolactone does not result from a muscular, renal or hepatic ammonia production but seems related to an increased intestinal ammoniagenesis which which is secondary to the bacterial hydrolysis of urea in the colon; indeed, there is a significant correlation between the ammonemia increase and the simultaneous rise in blood urea during treatment.

Adult↗
PubMed1978

Cross reactivity of digitoxin and spironolactone in two radioimmunoassays for serum digoxin.

We measured the cross reactivity of two medications--digitoxin and spironolactone--in two digoxin radioimmunoassay (liquid and solid-phase) kit procedures. Both tests showed similar average percentages of cross reactivity with digitoxin (7.2 and 8.9% for intravenous, and 11.9 and 10.9% for oral administration), but no cross reactivity with spironolactone or its metabolites after equal intravenous or oral doses.

Cross Reactions↗
PubMedDate not supplied

[Changes in the electrolyte balance and the transmural differential in the potentials of the blood vessel wall during the administration of spironolactone and its combination with euphylline].

It has been demonstrated in experiments on normotensive cats that during chronic administration of spironolactone alone or combined with euphylline there occur inconclusive variations in the transmural potential difference and electrolyte balance in the vascular wall. Spironolactone did not produce any marked changes in electrolyte balance and hypotensive effect. Combined administration of the drugs under study made the intima of the carotid artery electrically positive. By day 5 one can see a clear tendency to an increase in the biopotential towards electric negative, with the alterations in the sodium and potassium content in the vascular wall being the most pronounced.

Aminophylline↗
PubMed1983

Therapeutic effects of spironolactone in polycystic ovary syndrome.

The authors examined the effect of three months' treatment with spironolactone in 34 women with polycystic ovary syndrome. In all patients a significant decrease in hirsutism was noted as well as restoration of a regular although anovulatory menstrual pattern. Plasma luteinizing hormone and follicle-stimulating hormone levels remained unchanged after spironolactone treatment; however, prolactin levels were lowered in both women with normal and those with elevated basal levels. Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate levels were decreased after three months of therapy. No side effects were observed. Plasma electrolytes and liver function tests were normal during the entire time of treatment. This therapy is recommended as initial nontoxic but effective treatment for women with polycystic ovary syndrome who are hirsute and have menstrual disturbances.

Adult↗
PubMed1982

Effect of spironolactone on hepatic microsomal monooxygenase and azoreductase activities.

Spironolactone pretreatment (10mg/100g, twice daily for 4 days, orally) caused a significant decrease in cytochrome P-450 levels in the liver microsomes in female rats but male rats were unaffected. NADH oxidase activity was significantly decreased in both sexes by this pretreatment but NADPH oxidase and NADH cytochrome C reductase activities were not altered. NADPH cytochrome c reductase activity was increased more markedly in female rats. Despite the decrease in P-450 levels, aminopyrine N-demethylase activity was increased in female rats, while it remained unchanged in males. 7-Ethoxycoumarin O-deethylase activity was markedly increased in male and slightly decreased in female rats. The azoreductase activity was slightly reduced in treated male rats and remained unaltered in female rats when it was expressed in activity per mg microsomal protein, but the activity did show a significant increase in female rats when it was expressed as a P-450 specific rate. Sex associated differences in the effect of spironolactone on the rat liver microsomal drug metabolizing enzyme system demonstrated in the present study cannot be simply explained by the previously reported effect on adrenal and testicular steroids in male rats. It also seems unlikely that these effects were caused by an alteration in P-450 quality by selective destruction of certain species of P-450.

Aminopyrine N-Demethylase↗
PubMed1982

The bioavailability of spironolactone hydrochlorothiazide combination preparation.

In a single-blind, randomized cross-over study the bioavailability of Spironothiazid (50 mg spironolactone, 50 mg hydrochlorothiazide) was investigated in six healthy male volunteers by comparing the same dose of the well-established drugs Aldactone dragees, 50 mg, and Esidrex tablets, 25 mg. After 6 days treatment with 2 X 1 Spironothiazid or 2 X 1 Aldactone dragees, 50 mg, plus Esidrex tablets, 25 mg daly, orally, the serum concentrations and the cumulative renal excretion of the active substances were measured after the morning dose on the 7th day of the study. Canrenone (the main metabolite of spironolactone) was measured fluorimetrically, hydrochlorothiazide was determined by gas chromatography. There was no statistically significant difference between the investigated drugs, neither in the areas under the curves nor in the cumulative renal excretion, thus indicating an identical bioavailability.

Adult↗
PubMed1982

Comparison of azosemide and furosemide in ascitic patients without and during administration of spironolactone.

Clinical, pharmacodynamic, and renal effects of a new diuretic, azosemide, were studied and compared with those of furosemide. Graded single intravenous (100-1600 mg) or peroral (100-400 mg) doses were administered to six patients with ascites due to liver cirrhosis without and during basic treatment with spironolactone. A standard peroral dose (160 mg) of both diuretics was found to have similar effectiveness. There was no difference in the time-course of action as determined on the basis of 24-h urine volume, sodium excretion, and osmolal clearance in four patients during basic treatment with spironolactone. However, azosemide appeared to be more effective than furosemide in those patients in whom a dose-response curve was established. Unlike furosemide, azosemide was much more effective when given intravenously than orally. Our study confirmed that azosemide is a "loop diuretic" with renal sites of action similar to those of furosemide. However, it has a higher efficiency, probably due to the steeper dose-response relationship.

Administration, Oral↗
PubMed1981

Spironolactone bodies in aldosteronomas and in the attached adrenals. Enzyme histochemical study of 19 cases of primary aldosteronism and a case of aldosteronism due to bilateral diffuse hyperplasia of the zona glomerulosa.

The formation of spironolactone (S) bodies, eosinophilic laminated cytoplasmic inclusions, is induced in the aldosterone-producing cells of the human adrenal cortex after the administration of spironolactone. The aim of this study was to define the enzyme histochemical characteristics of S bodies, S-body-containing cells, and the apparently hyperplastic zona glomerulosa (zG) of adrenal tissues attached to aldosteronomas. S bodies were found in 14 of 19 aldosteronomas, in 10 of 19 adrenal tissues attached to aldosteronomas, and in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia. The S bodies themselves exhibited most intense 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity but did not exhibit glucose-6-phosphate dehydrogenase (G6PD), NADP-dependent isocitrate dehydrogenase (NADP-ICDH), or succinate dehydrogenase (SDH) activity, confirming histochemically the origin of S bodies in the smooth endoplasmic reticulum. In two adenomas, S bodies were found to be surrounded by reaction products of acid hydrolase but were not found in the other adenomas and the remaining adrenal tissues. S-body-containing cells, irrespective of being neoplastic or not, showed enhanced 3 beta HSD, G6PD, and NADP-ICDH activity and weak SDH activity (Type I pattern of enzyme activity). Though zG was hyperplastic in most of the adrenal tissues attached to the adenomas, zG cells that did not contain S bodies showed the opposite pattern (Type II pattern) of enzyme activity (ie, weak 3 beta HSD, G6PD, and NADP-ICDH activity and intense SDH activity), in contrast to those in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia (which showed the Type I pattern). The results are consistent with the view that hyperplastic zG cells, except S-body-containing cells, in the case of aldosteronoma are not hyperfunctioning. The latter cells may have enhanced but possibly abortive steroidogenic activity.

Adenoma↗
PubMed1981

Successful treatment of polycystic ovary syndrome with spironolactone or bromocriptine.

Marked improvement in the severe hypertension (250/150 mmHg) and hirsutism of a patient suffering from polycystic ovary syndrome was quickly achieved by the use of spironolactone 200 mg per day. Substitution of spironolactone with bromocriptine induced further amelioration of these symptoms and renewal of ovulatory cycles. These drugs may afford another mode of therapy in patients with polycystic ovary syndrome.

Adult↗
PubMed1981

[Spironolactone in digitalis-requiring cardiac insufficiency following pacemaker implantation].

In a retrospective study conducted in 213 patients with cardiac pacemakers having severe bradycardiac heart failure with oedema, the addition of the aldosterone-antagonist spironolactone to a diuretic therapy was shown to have a favourable influence on the degree of compensation. This has been confirmed in 26 patients under the conditions of a drug interruption period, and in 24 other patients, who were treated with spironolactone after being decompensated under the therapy with digitalis and diuretic or without diuretic. The application of triamterene with a thiazide did not show this positive effect.

Aged↗
PubMed1980

Treatment of refractory congestive heart failure and normokalemic hypochloremic alkalosis with acetazolamide and spironolactone.

Combination therapy with a loop diuretic and an aldosterone antagonist can produce normokalemic hypochloremic alkalosis, a complication not previously documented in the literature. This report describes 74 patients who had severe congestive heart failure treated with a combination of furosemide and spironolactone in whom this complication developed. Acetazolamide corrected the metabolic abnormality. The combination of furosemide and spironolactone with intermittent courses of acetazolamide was very effective in the treatment of severe congestive heart failure complicated by normokalemic hypochloremic alkalosis.

Acetazolamide↗
PubMed1994

Inhibitory effect of spironolactone on the contractions of the rabbit uterine horn and the human myometrial strip.

The spontaneous contractions of the rabbit uterine horns and the human myometrial strips were stimulated by oxytocin and buserelin acetate in isolated preparations. Spironolactone application to these models produced inhibitory effects on the contractions. It is concluded that spironolactone has inhibitory effect on the rabbit uterine horn and the human myometrial strip contractions.

Animals↗
PubMed1994

Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.

Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.

Adult↗